Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.2747A>T (p.Asn916Ile)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(6)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Conflicting classifications of pathogenicity
Uncertain significance(5); Likely benign(1)
Uncertain significance(5); Likely benign(1)
6
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.2747A>T (p.Asn916Ile)
Variation ID: 220573 Accession: VCV000220573.19
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43092784 (GRCh38) [ NCBI UCSC ] 17: 41244801 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline May 29, 2016 May 1, 2024 Dec 26, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.2747A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Asn916Ile missense NM_001407571.1:c.2534A>T NP_001394500.1:p.Asn845Ile missense NM_001407581.1:c.2747A>T NP_001394510.1:p.Asn916Ile missense NM_001407582.1:c.2747A>T NP_001394511.1:p.Asn916Ile missense NM_001407583.1:c.2747A>T NP_001394512.1:p.Asn916Ile missense NM_001407585.1:c.2747A>T NP_001394514.1:p.Asn916Ile missense NM_001407587.1:c.2744A>T NP_001394516.1:p.Asn915Ile missense NM_001407590.1:c.2744A>T NP_001394519.1:p.Asn915Ile missense NM_001407591.1:c.2744A>T NP_001394520.1:p.Asn915Ile missense NM_001407593.1:c.2747A>T NP_001394522.1:p.Asn916Ile missense NM_001407594.1:c.2747A>T NP_001394523.1:p.Asn916Ile missense NM_001407596.1:c.2747A>T NP_001394525.1:p.Asn916Ile missense NM_001407597.1:c.2747A>T NP_001394526.1:p.Asn916Ile missense NM_001407598.1:c.2747A>T NP_001394527.1:p.Asn916Ile missense NM_001407602.1:c.2747A>T NP_001394531.1:p.Asn916Ile missense NM_001407603.1:c.2747A>T NP_001394532.1:p.Asn916Ile missense NM_001407605.1:c.2747A>T NP_001394534.1:p.Asn916Ile missense NM_001407610.1:c.2744A>T NP_001394539.1:p.Asn915Ile missense NM_001407611.1:c.2744A>T NP_001394540.1:p.Asn915Ile missense NM_001407612.1:c.2744A>T NP_001394541.1:p.Asn915Ile missense NM_001407613.1:c.2744A>T NP_001394542.1:p.Asn915Ile missense NM_001407614.1:c.2744A>T NP_001394543.1:p.Asn915Ile missense NM_001407615.1:c.2744A>T NP_001394544.1:p.Asn915Ile missense NM_001407616.1:c.2747A>T NP_001394545.1:p.Asn916Ile missense NM_001407617.1:c.2747A>T NP_001394546.1:p.Asn916Ile missense NM_001407618.1:c.2747A>T NP_001394547.1:p.Asn916Ile missense NM_001407619.1:c.2747A>T NP_001394548.1:p.Asn916Ile missense NM_001407620.1:c.2747A>T NP_001394549.1:p.Asn916Ile missense NM_001407621.1:c.2747A>T NP_001394550.1:p.Asn916Ile missense NM_001407622.1:c.2747A>T NP_001394551.1:p.Asn916Ile missense NM_001407623.1:c.2747A>T NP_001394552.1:p.Asn916Ile missense NM_001407624.1:c.2747A>T NP_001394553.1:p.Asn916Ile missense NM_001407625.1:c.2747A>T NP_001394554.1:p.Asn916Ile missense NM_001407626.1:c.2747A>T NP_001394555.1:p.Asn916Ile missense NM_001407627.1:c.2744A>T NP_001394556.1:p.Asn915Ile missense NM_001407628.1:c.2744A>T NP_001394557.1:p.Asn915Ile missense NM_001407629.1:c.2744A>T NP_001394558.1:p.Asn915Ile missense NM_001407630.1:c.2744A>T NP_001394559.1:p.Asn915Ile missense NM_001407631.1:c.2744A>T NP_001394560.1:p.Asn915Ile missense NM_001407632.1:c.2744A>T NP_001394561.1:p.Asn915Ile missense NM_001407633.1:c.2744A>T NP_001394562.1:p.Asn915Ile missense NM_001407634.1:c.2744A>T NP_001394563.1:p.Asn915Ile missense NM_001407635.1:c.2744A>T NP_001394564.1:p.Asn915Ile missense NM_001407636.1:c.2744A>T NP_001394565.1:p.Asn915Ile missense NM_001407637.1:c.2744A>T NP_001394566.1:p.Asn915Ile missense NM_001407638.1:c.2744A>T NP_001394567.1:p.Asn915Ile missense NM_001407639.1:c.2747A>T NP_001394568.1:p.Asn916Ile missense NM_001407640.1:c.2747A>T NP_001394569.1:p.Asn916Ile missense NM_001407641.1:c.2747A>T NP_001394570.1:p.Asn916Ile missense NM_001407642.1:c.2747A>T NP_001394571.1:p.Asn916Ile missense NM_001407644.1:c.2744A>T NP_001394573.1:p.Asn915Ile missense NM_001407645.1:c.2744A>T NP_001394574.1:p.Asn915Ile missense NM_001407646.1:c.2738A>T NP_001394575.1:p.Asn913Ile missense NM_001407647.1:c.2738A>T NP_001394576.1:p.Asn913Ile missense NM_001407648.1:c.2624A>T NP_001394577.1:p.Asn875Ile missense NM_001407649.1:c.2621A>T NP_001394578.1:p.Asn874Ile missense NM_001407652.1:c.2747A>T NP_001394581.1:p.Asn916Ile missense NM_001407653.1:c.2669A>T NP_001394582.1:p.Asn890Ile missense NM_001407654.1:c.2669A>T NP_001394583.1:p.Asn890Ile missense NM_001407655.1:c.2669A>T NP_001394584.1:p.Asn890Ile missense NM_001407656.1:c.2669A>T NP_001394585.1:p.Asn890Ile missense NM_001407657.1:c.2669A>T NP_001394586.1:p.Asn890Ile missense NM_001407658.1:c.2669A>T NP_001394587.1:p.Asn890Ile missense NM_001407659.1:c.2666A>T NP_001394588.1:p.Asn889Ile missense NM_001407660.1:c.2666A>T NP_001394589.1:p.Asn889Ile missense NM_001407661.1:c.2666A>T NP_001394590.1:p.Asn889Ile missense NM_001407662.1:c.2666A>T NP_001394591.1:p.Asn889Ile missense NM_001407663.1:c.2669A>T NP_001394592.1:p.Asn890Ile missense NM_001407664.1:c.2624A>T NP_001394593.1:p.Asn875Ile missense NM_001407665.1:c.2624A>T NP_001394594.1:p.Asn875Ile missense NM_001407666.1:c.2624A>T NP_001394595.1:p.Asn875Ile missense NM_001407667.1:c.2624A>T NP_001394596.1:p.Asn875Ile missense NM_001407668.1:c.2624A>T NP_001394597.1:p.Asn875Ile missense NM_001407669.1:c.2624A>T NP_001394598.1:p.Asn875Ile missense NM_001407670.1:c.2621A>T NP_001394599.1:p.Asn874Ile missense NM_001407671.1:c.2621A>T NP_001394600.1:p.Asn874Ile missense NM_001407672.1:c.2621A>T NP_001394601.1:p.Asn874Ile missense NM_001407673.1:c.2621A>T NP_001394602.1:p.Asn874Ile missense NM_001407674.1:c.2624A>T NP_001394603.1:p.Asn875Ile missense NM_001407675.1:c.2624A>T NP_001394604.1:p.Asn875Ile missense NM_001407676.1:c.2624A>T NP_001394605.1:p.Asn875Ile missense NM_001407677.1:c.2624A>T NP_001394606.1:p.Asn875Ile missense NM_001407678.1:c.2624A>T NP_001394607.1:p.Asn875Ile missense NM_001407679.1:c.2624A>T NP_001394608.1:p.Asn875Ile missense NM_001407680.1:c.2624A>T NP_001394609.1:p.Asn875Ile missense NM_001407681.1:c.2624A>T NP_001394610.1:p.Asn875Ile missense NM_001407682.1:c.2624A>T NP_001394611.1:p.Asn875Ile missense NM_001407683.1:c.2624A>T NP_001394612.1:p.Asn875Ile missense NM_001407684.1:c.2747A>T NP_001394613.1:p.Asn916Ile missense NM_001407685.1:c.2621A>T NP_001394614.1:p.Asn874Ile missense NM_001407686.1:c.2621A>T NP_001394615.1:p.Asn874Ile missense NM_001407687.1:c.2621A>T NP_001394616.1:p.Asn874Ile missense NM_001407688.1:c.2621A>T NP_001394617.1:p.Asn874Ile missense NM_001407689.1:c.2621A>T NP_001394618.1:p.Asn874Ile missense NM_001407690.1:c.2621A>T NP_001394619.1:p.Asn874Ile missense NM_001407691.1:c.2621A>T NP_001394620.1:p.Asn874Ile missense NM_001407692.1:c.2606A>T NP_001394621.1:p.Asn869Ile missense NM_001407694.1:c.2606A>T NP_001394623.1:p.Asn869Ile missense NM_001407695.1:c.2606A>T NP_001394624.1:p.Asn869Ile missense NM_001407696.1:c.2606A>T NP_001394625.1:p.Asn869Ile missense NM_001407697.1:c.2606A>T NP_001394626.1:p.Asn869Ile missense NM_001407698.1:c.2606A>T NP_001394627.1:p.Asn869Ile missense NM_001407724.1:c.2606A>T NP_001394653.1:p.Asn869Ile missense NM_001407725.1:c.2606A>T NP_001394654.1:p.Asn869Ile missense NM_001407726.1:c.2606A>T NP_001394655.1:p.Asn869Ile missense NM_001407727.1:c.2606A>T NP_001394656.1:p.Asn869Ile missense NM_001407728.1:c.2606A>T NP_001394657.1:p.Asn869Ile missense NM_001407729.1:c.2606A>T NP_001394658.1:p.Asn869Ile missense NM_001407730.1:c.2606A>T NP_001394659.1:p.Asn869Ile missense NM_001407731.1:c.2606A>T NP_001394660.1:p.Asn869Ile missense NM_001407732.1:c.2606A>T NP_001394661.1:p.Asn869Ile missense NM_001407733.1:c.2606A>T NP_001394662.1:p.Asn869Ile missense NM_001407734.1:c.2606A>T NP_001394663.1:p.Asn869Ile missense NM_001407735.1:c.2606A>T NP_001394664.1:p.Asn869Ile missense NM_001407736.1:c.2606A>T NP_001394665.1:p.Asn869Ile missense NM_001407737.1:c.2606A>T NP_001394666.1:p.Asn869Ile missense NM_001407738.1:c.2606A>T NP_001394667.1:p.Asn869Ile missense NM_001407739.1:c.2606A>T NP_001394668.1:p.Asn869Ile missense NM_001407740.1:c.2603A>T NP_001394669.1:p.Asn868Ile missense NM_001407741.1:c.2603A>T NP_001394670.1:p.Asn868Ile missense NM_001407742.1:c.2603A>T NP_001394671.1:p.Asn868Ile missense NM_001407743.1:c.2603A>T NP_001394672.1:p.Asn868Ile missense NM_001407744.1:c.2603A>T NP_001394673.1:p.Asn868Ile missense NM_001407745.1:c.2603A>T NP_001394674.1:p.Asn868Ile missense NM_001407746.1:c.2603A>T NP_001394675.1:p.Asn868Ile missense NM_001407747.1:c.2603A>T NP_001394676.1:p.Asn868Ile missense NM_001407748.1:c.2603A>T NP_001394677.1:p.Asn868Ile missense NM_001407749.1:c.2603A>T NP_001394678.1:p.Asn868Ile missense NM_001407750.1:c.2606A>T NP_001394679.1:p.Asn869Ile missense NM_001407751.1:c.2606A>T NP_001394680.1:p.Asn869Ile missense NM_001407752.1:c.2606A>T NP_001394681.1:p.Asn869Ile missense NM_001407838.1:c.2603A>T NP_001394767.1:p.Asn868Ile missense NM_001407839.1:c.2603A>T NP_001394768.1:p.Asn868Ile missense NM_001407841.1:c.2603A>T NP_001394770.1:p.Asn868Ile missense NM_001407842.1:c.2603A>T NP_001394771.1:p.Asn868Ile missense NM_001407843.1:c.2603A>T NP_001394772.1:p.Asn868Ile missense NM_001407844.1:c.2603A>T NP_001394773.1:p.Asn868Ile missense NM_001407845.1:c.2603A>T NP_001394774.1:p.Asn868Ile missense NM_001407846.1:c.2603A>T NP_001394775.1:p.Asn868Ile missense NM_001407847.1:c.2603A>T NP_001394776.1:p.Asn868Ile missense NM_001407848.1:c.2603A>T NP_001394777.1:p.Asn868Ile missense NM_001407849.1:c.2603A>T NP_001394778.1:p.Asn868Ile missense NM_001407850.1:c.2606A>T NP_001394779.1:p.Asn869Ile missense NM_001407851.1:c.2606A>T NP_001394780.1:p.Asn869Ile missense NM_001407852.1:c.2606A>T NP_001394781.1:p.Asn869Ile missense NM_001407853.1:c.2534A>T NP_001394782.1:p.Asn845Ile missense NM_001407854.1:c.2747A>T NP_001394783.1:p.Asn916Ile missense NM_001407858.1:c.2747A>T NP_001394787.1:p.Asn916Ile missense NM_001407859.1:c.2747A>T NP_001394788.1:p.Asn916Ile missense NM_001407860.1:c.2744A>T NP_001394789.1:p.Asn915Ile missense NM_001407861.1:c.2744A>T NP_001394790.1:p.Asn915Ile missense NM_001407862.1:c.2546A>T NP_001394791.1:p.Asn849Ile missense NM_001407863.1:c.2624A>T NP_001394792.1:p.Asn875Ile missense NM_001407874.1:c.2543A>T NP_001394803.1:p.Asn848Ile missense NM_001407875.1:c.2543A>T NP_001394804.1:p.Asn848Ile missense NM_001407879.1:c.2537A>T NP_001394808.1:p.Asn846Ile missense NM_001407881.1:c.2537A>T NP_001394810.1:p.Asn846Ile missense NM_001407882.1:c.2537A>T NP_001394811.1:p.Asn846Ile missense NM_001407884.1:c.2537A>T NP_001394813.1:p.Asn846Ile missense NM_001407885.1:c.2537A>T NP_001394814.1:p.Asn846Ile missense NM_001407886.1:c.2537A>T NP_001394815.1:p.Asn846Ile missense NM_001407887.1:c.2537A>T NP_001394816.1:p.Asn846Ile missense NM_001407889.1:c.2537A>T NP_001394818.1:p.Asn846Ile missense NM_001407894.1:c.2534A>T NP_001394823.1:p.Asn845Ile missense NM_001407895.1:c.2534A>T NP_001394824.1:p.Asn845Ile missense NM_001407896.1:c.2534A>T NP_001394825.1:p.Asn845Ile missense NM_001407897.1:c.2534A>T NP_001394826.1:p.Asn845Ile missense NM_001407898.1:c.2534A>T NP_001394827.1:p.Asn845Ile missense NM_001407899.1:c.2534A>T NP_001394828.1:p.Asn845Ile missense NM_001407900.1:c.2537A>T NP_001394829.1:p.Asn846Ile missense NM_001407902.1:c.2537A>T NP_001394831.1:p.Asn846Ile missense NM_001407904.1:c.2537A>T NP_001394833.1:p.Asn846Ile missense NM_001407906.1:c.2537A>T NP_001394835.1:p.Asn846Ile missense NM_001407907.1:c.2537A>T NP_001394836.1:p.Asn846Ile missense NM_001407908.1:c.2537A>T NP_001394837.1:p.Asn846Ile missense NM_001407909.1:c.2537A>T NP_001394838.1:p.Asn846Ile missense NM_001407910.1:c.2537A>T NP_001394839.1:p.Asn846Ile missense NM_001407915.1:c.2534A>T NP_001394844.1:p.Asn845Ile missense NM_001407916.1:c.2534A>T NP_001394845.1:p.Asn845Ile missense NM_001407917.1:c.2534A>T NP_001394846.1:p.Asn845Ile missense NM_001407918.1:c.2534A>T NP_001394847.1:p.Asn845Ile missense NM_001407919.1:c.2624A>T NP_001394848.1:p.Asn875Ile missense NM_001407920.1:c.2483A>T NP_001394849.1:p.Asn828Ile missense NM_001407921.1:c.2483A>T NP_001394850.1:p.Asn828Ile missense NM_001407922.1:c.2483A>T NP_001394851.1:p.Asn828Ile missense NM_001407923.1:c.2483A>T NP_001394852.1:p.Asn828Ile missense NM_001407924.1:c.2483A>T NP_001394853.1:p.Asn828Ile missense NM_001407925.1:c.2483A>T NP_001394854.1:p.Asn828Ile missense NM_001407926.1:c.2483A>T NP_001394855.1:p.Asn828Ile missense NM_001407927.1:c.2483A>T NP_001394856.1:p.Asn828Ile missense NM_001407928.1:c.2483A>T NP_001394857.1:p.Asn828Ile missense NM_001407929.1:c.2483A>T NP_001394858.1:p.Asn828Ile missense NM_001407930.1:c.2480A>T NP_001394859.1:p.Asn827Ile missense NM_001407931.1:c.2480A>T NP_001394860.1:p.Asn827Ile missense NM_001407932.1:c.2480A>T NP_001394861.1:p.Asn827Ile missense NM_001407933.1:c.2483A>T NP_001394862.1:p.Asn828Ile missense NM_001407934.1:c.2480A>T NP_001394863.1:p.Asn827Ile missense NM_001407935.1:c.2483A>T NP_001394864.1:p.Asn828Ile missense NM_001407936.1:c.2480A>T NP_001394865.1:p.Asn827Ile missense NM_001407937.1:c.2624A>T NP_001394866.1:p.Asn875Ile missense NM_001407938.1:c.2624A>T NP_001394867.1:p.Asn875Ile missense NM_001407939.1:c.2624A>T NP_001394868.1:p.Asn875Ile missense NM_001407940.1:c.2621A>T NP_001394869.1:p.Asn874Ile missense NM_001407941.1:c.2621A>T NP_001394870.1:p.Asn874Ile missense NM_001407942.1:c.2606A>T NP_001394871.1:p.Asn869Ile missense NM_001407943.1:c.2603A>T NP_001394872.1:p.Asn868Ile missense NM_001407944.1:c.2606A>T NP_001394873.1:p.Asn869Ile missense NM_001407945.1:c.2606A>T NP_001394874.1:p.Asn869Ile missense NM_001407946.1:c.2414A>T NP_001394875.1:p.Asn805Ile missense NM_001407947.1:c.2414A>T NP_001394876.1:p.Asn805Ile missense NM_001407948.1:c.2414A>T NP_001394877.1:p.Asn805Ile missense NM_001407949.1:c.2414A>T NP_001394878.1:p.Asn805Ile missense NM_001407950.1:c.2414A>T NP_001394879.1:p.Asn805Ile missense NM_001407951.1:c.2414A>T NP_001394880.1:p.Asn805Ile missense NM_001407952.1:c.2414A>T NP_001394881.1:p.Asn805Ile missense NM_001407953.1:c.2414A>T NP_001394882.1:p.Asn805Ile missense NM_001407954.1:c.2411A>T NP_001394883.1:p.Asn804Ile missense NM_001407955.1:c.2411A>T NP_001394884.1:p.Asn804Ile missense NM_001407956.1:c.2411A>T NP_001394885.1:p.Asn804Ile missense NM_001407957.1:c.2414A>T NP_001394886.1:p.Asn805Ile missense NM_001407958.1:c.2411A>T NP_001394887.1:p.Asn804Ile missense NM_001407959.1:c.2366A>T NP_001394888.1:p.Asn789Ile missense NM_001407960.1:c.2366A>T NP_001394889.1:p.Asn789Ile missense NM_001407962.1:c.2363A>T NP_001394891.1:p.Asn788Ile missense NM_001407963.1:c.2366A>T NP_001394892.1:p.Asn789Ile missense NM_001407964.1:c.2603A>T NP_001394893.1:p.Asn868Ile missense NM_001407965.1:c.2243A>T NP_001394894.1:p.Asn748Ile missense NM_001407966.1:c.1859A>T NP_001394895.1:p.Asn620Ile missense NM_001407967.1:c.1859A>T NP_001394896.1:p.Asn620Ile missense NM_001407968.1:c.788-645A>T intron variant NM_001407969.1:c.788-645A>T intron variant NM_001407970.1:c.788-1752A>T intron variant NM_001407971.1:c.788-1752A>T intron variant NM_001407972.1:c.785-1752A>T intron variant NM_001407973.1:c.788-1752A>T intron variant NM_001407974.1:c.788-1752A>T intron variant NM_001407975.1:c.788-1752A>T intron variant NM_001407976.1:c.788-1752A>T intron variant NM_001407977.1:c.788-1752A>T intron variant NM_001407978.1:c.788-1752A>T intron variant NM_001407979.1:c.788-1752A>T intron variant NM_001407980.1:c.788-1752A>T intron variant NM_001407981.1:c.788-1752A>T intron variant NM_001407982.1:c.788-1752A>T intron variant NM_001407983.1:c.788-1752A>T intron variant NM_001407984.1:c.785-1752A>T intron variant NM_001407985.1:c.785-1752A>T intron variant NM_001407986.1:c.785-1752A>T intron variant NM_001407990.1:c.788-1752A>T intron variant NM_001407991.1:c.785-1752A>T intron variant NM_001407992.1:c.785-1752A>T intron variant NM_001407993.1:c.788-1752A>T intron variant NM_001408392.1:c.785-1752A>T intron variant NM_001408396.1:c.785-1752A>T intron variant NM_001408397.1:c.785-1752A>T intron variant NM_001408398.1:c.785-1752A>T intron variant NM_001408399.1:c.785-1752A>T intron variant NM_001408400.1:c.785-1752A>T intron variant NM_001408401.1:c.785-1752A>T intron variant NM_001408402.1:c.785-1752A>T intron variant NM_001408403.1:c.788-1752A>T intron variant NM_001408404.1:c.788-1752A>T intron variant NM_001408406.1:c.791-1761A>T intron variant NM_001408407.1:c.785-1752A>T intron variant NM_001408408.1:c.779-1752A>T intron variant NM_001408409.1:c.710-1752A>T intron variant NM_001408410.1:c.647-1752A>T intron variant NM_001408411.1:c.710-1752A>T intron variant NM_001408412.1:c.710-1752A>T intron variant NM_001408413.1:c.707-1752A>T intron variant NM_001408414.1:c.710-1752A>T intron variant NM_001408415.1:c.710-1752A>T intron variant NM_001408416.1:c.707-1752A>T intron variant NM_001408418.1:c.671-1752A>T intron variant NM_001408419.1:c.671-1752A>T intron variant NM_001408420.1:c.671-1752A>T intron variant NM_001408421.1:c.668-1752A>T intron variant NM_001408422.1:c.671-1752A>T intron variant NM_001408423.1:c.671-1752A>T intron variant NM_001408424.1:c.668-1752A>T intron variant NM_001408425.1:c.665-1752A>T intron variant NM_001408426.1:c.665-1752A>T intron variant NM_001408427.1:c.665-1752A>T intron variant NM_001408428.1:c.665-1752A>T intron variant NM_001408429.1:c.665-1752A>T intron variant NM_001408430.1:c.665-1752A>T intron variant NM_001408431.1:c.668-1752A>T intron variant NM_001408432.1:c.662-1752A>T intron variant NM_001408433.1:c.662-1752A>T intron variant NM_001408434.1:c.662-1752A>T intron variant NM_001408435.1:c.662-1752A>T intron variant NM_001408436.1:c.665-1752A>T intron variant NM_001408437.1:c.665-1752A>T intron variant NM_001408438.1:c.665-1752A>T intron variant NM_001408439.1:c.665-1752A>T intron variant NM_001408440.1:c.665-1752A>T intron variant NM_001408441.1:c.665-1752A>T intron variant NM_001408442.1:c.665-1752A>T intron variant NM_001408443.1:c.665-1752A>T intron variant NM_001408444.1:c.665-1752A>T intron variant NM_001408445.1:c.662-1752A>T intron variant NM_001408446.1:c.662-1752A>T intron variant NM_001408447.1:c.662-1752A>T intron variant NM_001408448.1:c.662-1752A>T intron variant NM_001408450.1:c.662-1752A>T intron variant NM_001408451.1:c.653-1752A>T intron variant NM_001408452.1:c.647-1752A>T intron variant NM_001408453.1:c.647-1752A>T intron variant NM_001408454.1:c.647-1752A>T intron variant NM_001408455.1:c.647-1752A>T intron variant NM_001408456.1:c.647-1752A>T intron variant NM_001408457.1:c.647-1752A>T intron variant NM_001408458.1:c.647-1752A>T intron variant NM_001408459.1:c.647-1752A>T intron variant NM_001408460.1:c.647-1752A>T intron variant NM_001408461.1:c.647-1752A>T intron variant NM_001408462.1:c.644-1752A>T intron variant NM_001408463.1:c.644-1752A>T intron variant NM_001408464.1:c.644-1752A>T intron variant NM_001408465.1:c.644-1752A>T intron variant NM_001408466.1:c.647-1752A>T intron variant NM_001408467.1:c.647-1752A>T intron variant NM_001408468.1:c.644-1752A>T intron variant NM_001408469.1:c.647-1752A>T intron variant NM_001408470.1:c.644-1752A>T intron variant NM_001408472.1:c.788-1752A>T intron variant NM_001408473.1:c.785-1752A>T intron variant NM_001408474.1:c.587-1752A>T intron variant NM_001408475.1:c.584-1752A>T intron variant NM_001408476.1:c.587-1752A>T intron variant NM_001408478.1:c.578-1752A>T intron variant NM_001408479.1:c.578-1752A>T intron variant NM_001408480.1:c.578-1752A>T intron variant NM_001408481.1:c.578-1752A>T intron variant NM_001408482.1:c.578-1752A>T intron variant NM_001408483.1:c.578-1752A>T intron variant NM_001408484.1:c.578-1752A>T intron variant NM_001408485.1:c.578-1752A>T intron variant NM_001408489.1:c.578-1752A>T intron variant NM_001408490.1:c.575-1752A>T intron variant NM_001408491.1:c.575-1752A>T intron variant NM_001408492.1:c.578-1752A>T intron variant NM_001408493.1:c.575-1752A>T intron variant NM_001408494.1:c.548-1752A>T intron variant NM_001408495.1:c.545-1752A>T intron variant NM_001408496.1:c.524-1752A>T intron variant NM_001408497.1:c.524-1752A>T intron variant NM_001408498.1:c.524-1752A>T intron variant NM_001408499.1:c.524-1752A>T intron variant NM_001408500.1:c.524-1752A>T intron variant NM_001408501.1:c.524-1752A>T intron variant NM_001408502.1:c.455-1752A>T intron variant NM_001408503.1:c.521-1752A>T intron variant NM_001408504.1:c.521-1752A>T intron variant NM_001408505.1:c.521-1752A>T intron variant NM_001408506.1:c.461-1752A>T intron variant NM_001408507.1:c.461-1752A>T intron variant NM_001408508.1:c.452-1752A>T intron variant NM_001408509.1:c.452-1752A>T intron variant NM_001408510.1:c.407-1752A>T intron variant NM_001408511.1:c.404-1752A>T intron variant NM_001408512.1:c.284-1752A>T intron variant NM_001408513.1:c.578-1752A>T intron variant NM_001408514.1:c.578-1752A>T intron variant NM_007297.4:c.2606A>T NP_009228.2:p.Asn869Ile missense NM_007298.4:c.788-1752A>T intron variant NM_007299.4:c.788-1752A>T intron variant NM_007300.4:c.2747A>T NP_009231.2:p.Asn916Ile missense NR_027676.1:n.2883A>T NC_000017.11:g.43092784T>A NC_000017.10:g.41244801T>A NG_005905.2:g.125200A>T LRG_292:g.125200A>T LRG_292t1:c.2747A>T LRG_292p1:p.Asn916Ile - Protein change
- N916I, N869I, N620I, N804I, N848I, N846I, N875I, N889I, N748I, N788I, N805I, N845I, N849I, N868I, N890I, N915I, N789I, N827I, N828I, N874I, N913I
- Other names
- -
- Canonical SPDI
- NC_000017.11:43092783:T:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13029 | 14833 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Dec 26, 2023 | RCV000205469.10 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Sep 19, 2016 | RCV000409651.3 | |
| Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Sep 15, 2023 | RCV000218038.9 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Feb 24, 2020 | RCV001562678.3 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Likely benign
(Mar 23, 2023)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV003849375.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023
Comment:
BRCA1 coldspot (exon 11 using historical exon numbering). Reclassification based on statistical prior probability
|
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
|
|
|
Uncertain significance
(Dec 26, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000261220.8
First in ClinVar: Feb 02, 2016 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 916 of the BRCA1 protein (p.Asn916Ile). … (more)
This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 916 of the BRCA1 protein (p.Asn916Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 220573). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
|
|
|
Uncertain significance
(Sep 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000276430.5
First in ClinVar: May 29, 2016 Last updated: May 01, 2024 |
Comment:
The p.N916I variant (also known as c.2747A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide … (more)
The p.N916I variant (also known as c.2747A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 2747. The asparagine at codon 916 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
|
|
Uncertain significance
(Oct 07, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV004360257.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces asparagine with isoleucine at codon 916 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure … (more)
This missense variant replaces asparagine with isoleucine at codon 916 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
|
|
|
Uncertain significance
(Sep 19, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000489323.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 24, 2022 |
|
|
|
Uncertain significance
(Feb 24, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001785482.1
First in ClinVar: Aug 14, 2021 Last updated: Aug 14, 2021 |
Comment:
Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not … (more)
Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge (less)
|
Comment:
Comment:
This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 916 of the BRCA1 protein (p.Asn916Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 220573). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Comment:
The p.N916I variant (also known as c.2747A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 2747. The asparagine at codon 916 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
This missense variant replaces asparagine with isoleucine at codon 916 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Comment:
Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Comment:
This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 916 of the BRCA1 protein (p.Asn916Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 220573). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Comment:
The p.N916I variant (also known as c.2747A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 2747. The asparagine at codon 916 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
This missense variant replaces asparagine with isoleucine at codon 916 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Comment:
Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots". | Dines JN | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 31911673 |
Text-mined citations for rs864622588 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.